Dopaminergic modulation of arousal in Drosophila
Dopaminergic modulation of arousal in Drosophila
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DOI：
10.1016/j.cub.2005.05.025
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发表时间：
2005-07-12
期刊：
影响因子：
9.2
通讯作者：
Greenspan, RJ
中科院分区：
文献类型：
--
作者：
Andretic, R;van Swinderen, B;Greenspan, RJ
背景：大脑的唤醒水平设定了从简单到复杂的行为阈值。然而，人们对包括唤醒在内的各种现象的机制基础仍然知之甚少。研究人员对果蝇的行为进行了研究，涵盖了从睡眠到视觉感知再到精神刺激反应的不同唤醒水平。结果：我们通过行为、遗传、药理学和电生理学相结合的方法研究了果蝇大脑中唤醒的神经生物学机制。服用甲基苯丙胺 (METH) 会抑制睡眠并促进活跃的觉醒，而多巴胺合成抑制剂则会促进睡眠。冰毒通过增加性唤起同时降低成功的性表现来影响求爱行为。野生型果蝇内侧原大脑的电生理记录表明，摄入冰毒会对与视觉刺激感知相关的大脑反应产生快速且有害的影响。基因操纵动物的记录表明，这些反应需要多巴胺能传递，并且多巴胺能传递减弱引起的视觉处理缺陷可以通过冰毒来挽救。结论：我们表明，多巴胺水平的变化对不同复杂性行为的唤醒有不同的影响。根据哺乳动物大脑中多巴胺作用的倒U型假说，当多巴胺水平过高或过低时，复杂的行为（例如视觉感知）就会退化。更简单的行为，例如睡眠和运动，会随着多巴胺水平的变化而表现出分级反应。
Background: Arousal levels in the brain set thresholds for behavior, from simple to complex. The mechanistic underpinnings of the various phenomena comprising arousal, however, are still poorly understood. Drosophila behaviors have been studied that span different levels of arousal, from sleep to visual perception to psychostimulant responses.Results: We have investigated neurobiological mechanisms of arousal in the Drosophila brain by a combined behavioral, genetic, pharmacological, and electrophysiological approach. Administration of methamphetamine (METH) suppresses sleep and promotes active wakefulness, whereas an inhibitor of dopamine synthesis promotes sleep. METH affects courtship behavior by increasing sexual arousal while decreasing successful sexual performance. Electrophysiological recordings from the medial protocerebrum of wild-type flies showed that METH ingestion has rapid and detrimental effects on a brain response associated with perception of visual stimuli. Recordings in genetically manipulated animals show that dopaminergic transmission is required for these responses and that visual-processing deficits caused by attenuated dopaminergic transmission can be rescued by METH.Conclusions: We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.